Matrix proteoglycans are markedly affected in advanced laryngeal squamous cell carcinoma

AbstractProteoglycans (PGs) are implicated in the growth and progression of malignant tumors. In this study, we examined the concentration and localization of PGs in advanced (stage IV) laryngeal squamous cell carcinoma (LSCC) and compared with human normal larynx (HNL). LSCC and HNL sections were examined immunohistochemically with a panel of antibodies, and tissues extracts were analyzed by biochemical methods including immunoblotting and high performance liquid chromatography (HPLC). The results demonstrated significant destruction of cartilage in LSCC, which was followed by marked decrease of aggrecan and link protein. In contrast to the loss of aggrecan in LSCC, accumulation of versican and decorin was observed in the tumor-associated stroma. Biochemical analyses indicated that aggrecan, versican, decorin and biglycan comprise the vast majority of total PGs in both healthy and cancerous tissue. In LSCC the absolute amounts of KS/CS/DS-containing PGs were dramatically decreased about 18-fold in comparison to HNL. This decrease is due to the loss of aggrecan. Disaccharide analysis of CS/DSPGs from LSCC showed a significant reduction of 6-sulfated Δ-disaccharides (Δdi-6S) with a parallel increase of 4-sulfated Δ-disaccharides (Δdi-4S) as compared to HNL. The obtained data clearly demonstrate that tumor progression is closely related to specific alteration of matrix PGs in LSCC. The altered composition of PGs in cartilage, as well as in tumor-associated stroma, is crucial for the biological behaviour of cancer cells in the diseased tissue

IGF-IR cooperates with ERα to inhibit breast cancer cell aggressiveness by regulating the expression and localisation of ECM molecules

IGF-IR is highly associated with the behaviour of breast cancer cells. In ERα-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERα-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules. In particular, activation of IGF-IR, but not EGFR, in MCF-7 breast cancer cells results in the reduction of specific matrix metalloproteinases and their inhibitors. In contrast, IGF-IR inhibition leads to the depletion by endocytosis of syndecan-4. Global important changes in cell adhesion receptors, which include integrins and syndecan-4 triggered by IGF-IR inhibition, regulate adhesion and invasion. Cell function assays that were performed in MCF-7 cells as well as their ERα-suppressed counterparts indicate that ER status is a major determinant of IGF-IR regulatory role on cell adhesion and invasion. The strong inhibitory role of IGF-IR on breast cancer cells aggressiveness for which E2-ERα signaling pathway seems to be essential, highlights IGF-IR as a major molecular target for novel therapeutic strategies

A Simple Separable Exact C*-Algebra not Anti-isomorphic to Itself

We give an example of an exact, stably finite, simple. separable C*-algebra D which is not isomorphic to its opposite algebra. Moreover, D has the following additional properties. It is stably finite, approximately divisible, has real rank zero and stable rank one, has a unique tracial state, and the order on projections over D is determined by traces. It also absorbs the Jiang-Su algebra Z, and in fact absorbs the 3^{\infty} UHF algebra. We can also explicitly compute the K-theory of D, namely K_0 (D) = Z[1/3] with the standard order, and K_1 (D) = 0, as well as the Cuntz semigroup of D.Comment: 16 pages; AMSLaTeX. The material on other possible K-groups for such an algebra has been moved to a separate paper (1309.4142 [math.OA]

A Short Survey of Noncommutative Geometry

We give a survey of selected topics in noncommutative geometry, with some emphasis on those directly related to physics, including our recent work with Dirk Kreimer on renormalization and the Riemann-Hilbert problem. We discuss at length two issues. The first is the relevance of the paradigm of geometric space, based on spectral considerations, which is central in the theory. As a simple illustration of the spectral formulation of geometry in the ordinary commutative case, we give a polynomial equation for geometries on the four dimensional sphere with fixed volume. The equation involves an idempotent e, playing the role of the instanton, and the Dirac operator D. It expresses the gamma five matrix as the pairing between the operator theoretic chern characters of e and D. It is of degree five in the idempotent and four in the Dirac operator which only appears through its commutant with the idempotent. It determines both the sphere and all its metrics with fixed volume form. We also show using the noncommutative analogue of the Polyakov action, how to obtain the noncommutative metric (in spectral form) on the noncommutative tori from the formal naive metric. We conclude on some questions related to string theory.Comment: Invited lecture for JMP 2000, 45

Assembly maps with coefficients in topological algebras and the integral K-theoretic Novikov conjecture

We prove that any countable discrete and torsion free subgroup of a general linear group over an arbitrary field or a similar subgroup of an almost connected Lie group satisfies the integral algebraic K-theoretic (split) Novikov conjecture over \cpt and \S, where \cpt denotes the C^*-algebra of compact operators and \S denotes the algebra of Schatten class operators. We introduce assembly maps with finite coefficients and under an additional hypothesis, we prove that such a group also satisfies the algebraic K-theoretic Novikov conjecture over \bar{\mathbb{Q}} and \mathbb{C} with finite coefficients. For all torsion free Gromov hyperbolic groups G, we demonstrate that the canonical algebra homomorphism \cpt[G]\map C^*_r(G)\hat{\otimes}\cpt induces an isomorphism between their algebraic K-theory groups.Comment: v2 Exposition improved; one lemma and grant acknowledgement added; v3 some terminology changed and details added, Theorems 4.5 and 4.7 in v3 need an extra hypothesis; v4 abridged version accepted for publication in JHR

Cartan subalgebras and the UCT problem, II

We show that outer approximately represenbtable actions of a finite cyclic group on UCT Kirchberg algebras satisfy a certain quasi-freeness type property if the corresponding crossed products satisfy the UCT and absorb a suitable UHF algebra tensorially. More concretely, we prove that for such an action there exists an inverse semigroup of homogeneous partial isometries that generates the ambient C*-algebra and whose idempotent semilattice generates a Cartan subalgebra. We prove a similar result for actions of finite cyclic groups with the Rokhlin property on UCT Kirchberg algebras absorbing a suitable UHF algebra. These results rely on a new construction of Cartan subalgebras in certain inductive limits of Cartan pairs. We also provide a characterisation of the UCT problem in terms of finite order automorphisms, Cartan subalgebras and inverse semigroups of partial isometries of the Cuntz algebra $\mathcal{O}_2$. This generalizes earlier work of the authors.Comment: minor revisions; final version, accepted for publication in Math. Ann.; 26 page

Versican but not decorin accumulation is related to malignancy in mammographically detected high density and malignant-appearing microcalcifications in non-palpable breast carcinomas

<p>Abstract</p> <p>Background</p> <p>Mammographic density (MD) and malignant-appearing microcalcifications (MAMCs) represent the earliest mammographic findings of non-palpable breast carcinomas. Matrix proteoglycans versican and decorin are frequently over-expressed in various malignancies and are differently involved in the progression of cancer. In the present study, we have evaluated the expression of versican and decorin in non-palpable breast carcinomas and their association with high risk mammographic findings and tumor characteristics.</p> <p>Methods</p> <p>Three hundred and ten patients with non-palpable suspicious breast lesions, detected during screening mammography, were studied. Histological examination was carried out and the expression of decorin, versican, estrogen receptor α (ERα), progesterone receptor (PR) and c-erbB2 (HER-2/neu) was assessed by immunohistochemistry.</p> <p>Results</p> <p>Histological examination showed 83 out of 310 (26.8%) carcinomas of various subtypes. Immunohistochemistry was carried out in 62/83 carcinomas. Decorin was accumulated in breast tissues with MD and MAMCs independently of the presence of malignancy. In contrast, versican was significantly increased only in carcinomas with MAMCs (median ± SE: 42.0 ± 9.1) and MD (22.5 ± 10.1) as compared to normal breast tissue with MAMCs (14.0 ± 5.8), MD (11.0 ± 4.4) and normal breast tissue without mammographic findings (10.0 ± 2.0). Elevated levels of versican were correlated with higher tumor grade and invasiveness in carcinomas with MD and MAMCs, whereas increased amounts of decorin were associated with <it>in situ </it>carcinomas in MAMCs. Stromal deposition of both proteoglycans was related to higher expression of ERα and PR in tumor cells only in MAMCs.</p> <p>Conclusions</p> <p>The specific accumulation of versican in breast tissue with high MD and MAMCs only in the presence of malignant transformation and its association with the aggressiveness of the tumor suggests its possible use as molecular marker in non-palpable breast carcinomas.</p

Spt2p Defines a New Transcription-Dependent Gross Chromosomal Rearrangement Pathway

Large numbers of gross chromosomal rearrangements (GCRs) are frequently observed in many cancers. High mobility group 1 (HMG1) protein is a non-histone DNA-binding protein and is highly expressed in different types of tumors. The high expression of HMG1 could alter DNA structure resulting in GCRs. Spt2p is a non-histone DNA binding protein in Saccharomyces cerevisiae and shares homology with mammalian HMG1 protein. We found that Spt2p overexpression enhances GCRs dependent on proteins for transcription elongation and polyadenylation. Excess Spt2p increases the number of cells in S phase and the amount of single-stranded DNA (ssDNA) that might be susceptible to cause DNA damage and GCR. Consistently, RNase H expression, which reduces levels of ssDNA, decreased GCRs in cells expressing high level of Spt2p. Lastly, high transcription in the chromosome V, the location at which GCR is monitored, also enhanced GCR formation. We propose a new pathway for GCR where DNA intermediates formed during transcription can lead to genomic instability